Efficacy and toxicity of once versus twice daily regimens of amikacin in febrile neutropenic pediatric cancer patients

Abstract

Purpose: To compare the pharmacokinetic profile, clinical efficacy and toxicity of once-daily dosing of amikacin compared to twice-daily dosing among pediatric cancer patients with fever and neutropenia. Methods: 134 pediatric patients with hematological malignancies were randomly assigned to receive 15 mg/kg/day amikacin intravenously, either once or twice-daily dosing. For pharmacokinetics, two blood samples were obtained from each patient, the first sample was taken after 1 h from the beginning of infusion and the second sample was taken after 3 h from the first sample. Treatment success was considered when the patient improved without a change in the assigned antibiotic regimen or mortality from infection. Nephrotoxicity was assessed by following the increase in serum creatinine level. Results: Pharmacokinetic data revealed superiority in once-daily dosing where maximum concentration Cmax, area under the concentration time curve in 24 h AUC24 and elimination half-life t1/2 were a significantly higher while minimum concentration Cmin, elimination rate constant Ke and clearance CL were significantly lower in once-daily dosing compared to the twice-daily dosing. Clinical response achieved in 76.8% in once-daily group compared to 69.2% in twice-daily group. Nephrotoxicity was recorded in two patients in once-daily group and six patients in the twice-daily group. After stratifying our patients according to age, a significant increase was observed in the volume of distribution V and CL in pediatrics with age ⩽five compared to >five years. Cmax and AUC24 were significantly lower in the age group of ⩽five years. Conclusions: Clinical efficacy and nephrotoxicity were slightly improved in once-daily dosing compared to twice-daily dosing.

Keywords

• Amikacin
• Once-daily dosing
• Twice-daily dosing
• Febrile neutropenia